Composition and dressing for wound treatment

ABSTRACT

The invention provides methods and compositions for wound treatment and/or blood clot formation, e.g., arresting the flow of blood from an open wound. The methods and compositions provide for promoting and accelerating wound healing and optionally provide for inhibition of microbial infection and/or a local analgesic effect.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.14/344,403, filed on Mar. 12, 2014, which is a national stageapplication of International Application No. PCT/US2012/054928, filed onSep. 12, 2012, which claims the benefit of priority from U.S.Provisional Application No. 61/670,251, filed on Jul. 11, 2012, and U.S.Provisional Application No. 61/533,484, filed on Sep. 12, 2011, thecontents of which applications are incorporated by reference herein intheir entirety.

BACKGROUND

Traditional hemostatic materials include tourniquets, bandages andsterilized dressings. Other hemostatic materials include fibrin glues(FG), oxidized celluloses (OC), oxidized regenerated celluloses (ORC)and mineral zeolite-based hemostats. Fibrin glues are hemostaticadhesives that are biocompatible, and which likely mimic the spontaneouscoagulation process while being independent of platelets and coagulationfactors. Commercially available fibrin-based glue products includeBeriplast P, Hemaseel, Biocol, Boheal and Quixil, etc. However, fibringlues are costly to produce, may be a source of blood-borne diseases andinfections, are complicated to apply and are slow in arresting bleeding.

Oxidized celluloses and oxidized regenerated celluloses are degradable,have antibacterial and hemostatic properties, and are especiallyeffective in arresting slow bleeding. The hemostatic mechanism withthese materials is proposed to be that the acidic carboxyl group in themolecule binds with the Fe³⁺ ion in the hemoglobin to generate theacidic Fe³⁺-hemin in blood, whereby red-brown gel blocks are formed toclose the end of capillaries thereby arresting the bleeding.Nevertheless, the oxidized celluloses and oxidized regeneratedcelluloses may expand, which in turn may cause neurothlipsis. Examplesof commercially available OC and ORC hemostats include the Oxycel seriesand the Surgicel series.

Inert mineral zeolite particles were first found to have a hemostaticeffect in the 1980s (see U.S. Pat. No. 4,822,349). In 2002, Z-MedicaCorporation produced a type of new hemostatic material under the name ofQuikClot™. These zeolite-based materials are apparently superior toother hemostatic materials in hemostatic efficacy. The hemostaticmechanism of mineral zeolites mainly resides in their extraordinaryselective adsorption of water relative to erythrocytes, platelets andother coagulation factors, which leads to a quick hemostasis byconcentrating the clotting factors at the injury site. However, mineralzeolite hemostats may be recognized as “foreign” and are notbiodegradable.

SUMMARY OF THE INVENTION

The invention provides methods and compositions to reduce or arrest theflow of blood from a wound, e.g., by accelerating clotting, andoptionally preventing or inhibiting microbial infection in the woundarea, and optionally providing for an analgesic effect in the woundarea, or any combination thereof. In one embodiment, the inventionprovides a substrate, e.g., a protective covering for a wound comprisinga composition of the invention. The compositions of the inventionpromote and accelerate healing as a result of the presence of acombination of agents. In one embodiment, the composition includes anabsorbent agent, such as mullite or aluminum silicate, and a bloodvessel constricting agent, such as aluminum sulfate or caffeine. Thecomposition may also include a blood clotting agent, e.g. fibrin, in aneffective amount. In another embodiment, the composition includes ablood vessel constricting agent, e.g., aluminum sulfate or caffeine, anda blood clotting agent in an effective amount. In one embodiment, theinvention provides an anhydrous mixture, e.g., in powder form,comprising a combination of agents forming a composition of theinvention. Compositions of the invention can be hydrated in the presenceof blood, wound exudate, or other selected liquid or aqueous media whichpromotes clotting of the blood. In one embodiment, the inventionprovides a gel comprising a composition of the invention. In oneembodiment, the invention provides an aerosol comprising a compositionof the invention.

In one embodiment, the invention provides a support, e.g., a bandage orother wound dressing, that includes an absorbent agent (e.g. mullite)and a blood vessel constricting agent, and optionally an antisepticagent such as an antimicrobial agent, optionally a topical analgesic oranesthetic agent, optionally isolated fibrin or components that yieldfibrin, e.g., isolated fibrinogen and isolated thrombin, or anycombination of optional component(s). In one embodiment, the inventionprovides a support that includes a blood vessel constricting agent andisolated fibrin or components that yield fibrin, e.g., isolatedfibrinogen and isolated thrombin, and optionally an antiseptic agentsuch as an antimicrobial agent, and optionally a topical analgesic oranesthetic agent.

Thus, in one embodiment the invention provides a composition for woundhealing comprising an amount of aluminum sulfate and an amount ofmullite. The composition may also include an amount of a blood clottingagent. In one embodiment, the composition is in powder form. In oneembodiment, the composition is in aerosol form. In one embodiment, thecomposition is in gel form.

In one embodiment, the composition is applied to a support, e.g., abandage. The composition may further include a local anesthetic agentand/or an antiseptic such as an antimicrobial agent.

In another embodiment, the invention provides a composition for woundhealing comprising an amount of aluminum sulfate and an amount of fibrinor an amount of fibrinogen and thrombin. In one embodiment, thecomposition is in powder form. In one embodiment, the composition is inaerosol form. In one embodiment, the composition is in gel form. In oneembodiment, the composition is applied to a support, e.g., a bandage.The composition may further include a local anesthetic agent and/or anantiseptic such as an antimicrobial agent.

In another embodiment, the invention provides a composition for woundhealing comprising an amount of mullite. The composition may be in anyform which may effectively deliver mullite to a wound, such as a powderform, an aerosol form, or a gel form. In one embodiment, the compositionis applied to a support, e.g., a bandage. The composition may furtherinclude a blood vessel constricting agent, such as aluminum sulfate, ablood clotting agent, such as fibrin, a local anesthetic agent, and/oran antiseptic such as an antimicrobial agent.

In one embodiment, a composition of the invention comprises a gelcomprising an absorbent agent and a blood vessel constricting agent, andoptionally an antiseptic agent such as an antimicrobial agent,optionally a topical analgesic or anesthetic agent, optionally isolatedfibrin or components that yield fibrin, e.g., isolated fibrinogen andisolated thrombin, or any combination of optional components. In oneembodiment, a composition of the invention comprises a gel comprising ablood constricting agent and isolated fibrin or components that yieldfibrin, e.g., isolated fibrinogen and isolated thrombin, and optionallyan antiseptic agent such as an antimicrobial agent, and optionally atopical analgesic or anesthetic agent.

In one embodiment, a composition of the invention comprises an aqueousliquid comprising an absorbent agent (e.g. mullite) and a blood vesselconstricting agent, and optionally an antiseptic agent such as anantimicrobial agent, optionally a topical analgesic or anesthetic agent,optionally isolated fibrin or components that yield fibrin, e.g.,isolated fibrinogen and isolated thrombin, or any combination ofoptional component(s). In another embodiment, a composition of theinvention comprises an aqueous liquid comprising a blood vesselconstricting agent and isolated fibrin or components that yield fibrin,e.g., isolated fibrinogen and isolated thrombin, and optionally anantiseptic agent such as an antimicrobial agent, and optionally atopical analgesic or anesthetic agent.

In one embodiment, the composition of the invention is a solid, e.g., apowder form. In another embodiment, the composition of the inventioncomprises an aerosol or spray having an absorbent agent (e.g. mullite)and a blood vessel constricting agent, and optionally an antisepticagent such as an antimicrobial agent, optionally a topical analgesic oranesthetic agent, optionally isolated fibrin or components that yieldfibrin, e.g., isolated fibrinogen and isolated thrombin, or a bloodvessel constricting agent and isolated fibrin or components that yieldfibrin, e.g., isolated fibrinogen and isolated thrombin, and optionallyan antiseptic agent such as an antimicrobial agent, and optionally atopical analgesic or anesthetic agent. In one embodiment, asubstantially anhydrous composition of the invention is provided. Acomposition of the invention may be applied as a powder, a liquid, anaerosol or spray, or a dry support, e.g., dressing, having a compositionof the invention applied thereto and/or embedded therein.

Also provided are methods of making and using the compositions andsupports having the compositions of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to devices, e.g., supports such as bandages, andcompositions, e.g., gels, aqueous liquids, powders and sprays, tofacilitate the reduction in bleeding, to initiate and provide forhemostasis and/or methods of making and using the devices andcompositions.

In one embodiment, the invention provides a support, e.g., a bandage orother wound dressing comprising an amount of a blood vessel constrictingagent and an amount of isolated fibrin or components that yield fibrin,e.g., isolated fibrinogen and isolated thrombin, optionally an adsorbentor absorbent agent, optionally an antiseptic agent such as anantimicrobial agent, optionally a topical analgesic or anesthetic agent,or any combination of optional components. In another embodiment, theinvention provides a support comprising an amount of a blood vesselconstricting agent and an amount of an absorbent agent, optionally anamount of isolated fibrin or components that yield fibrin, optionally anantiseptic agent, optionally a topical analgesic or anesthetic agent, orany combination of optional components. A “wound dressing” includes anypharmaceutically acceptable wound covering or support matrix such as,for example, a film, including those of a semipermeable or asemi-occlusive nature such as polyurethane copolymers, acrylamides,acrylates, paraffin, polysaccharides, cellophane and lanolin, andhydrocolloids including carboxymethylcellulose, protein constituents ofgelatin, pectin, and complex polysaccharides including Acacia gum, guargum and karaya. These materials may be utilized in the form of aflexible foam or, in the alternative, formulated in polyurethane or, ina further alternative, formulated as an adhesive mass such aspolyisobutylene; starch or propylene glycol; which typically containabout 80% to about 90% water and are conventionally formulated assheets, powders, pastes and gels in conjunction with cross-linkedpolymers such as polyethylene oxide, polyvinyl pyrollidone, acrylamide,propylene glycol; a foam such as polysaccharide which consist of ahydrophilic open-celled contact surface and hydrophobic closed-cellpolyurethane, and other materials including pine mesh gauze, paraffinand lanolin-coated gauze, polyethylene glycol-coated gauze, knittedviscose, rayon, and polyester and cellulose-like polysaccharide such asalginates, including calcium alginate, which may be formulated asnon-woven composites of fibers or spun into woven composites.

In one embodiment, the invention provides a device for promoting theclotting of blood, thereby controlling bleeding. The device comprises agauze substrate, e.g., cotton cellulose formed as woven or non-wovengauze, and a composition of the invention disposed on the gauzesubstrate. Upon the application of the device to the bleeding wound, atleast a portion of the components of the composition comes into contactwith the blood to cause the hemostatic effect. In another embodiment,the bandage has a flexible substrate and a gauze substrate mountedthereon.

According to another aspect, the invention provides a wound dressing,such as a bandage that can be applied to a bleeding wound to promote theclotting of blood, thereby controlling bleeding. In one embodiment, thebandage comprises a substrate, a mesh mounted on the substrate, and acomposition of the invention retained in the mesh. The mesh has aplurality of members arranged to define openings that allow for the flowof blood into the mesh and into the composition of the invention,thereby producing a clotting effect.

In one embodiment, a patch bandage comprises an absorbent fiber padwhich is backed up by and located at the center of a holding strip, thepad having a composition of the invention applied to the surface and/orembedded therein and the strip having an adhesive surface with the padbeing affiliated to the surface. The bandage may be placed over a cut orwound to cover the wound with the pad covering the wound to permit thepad to absorb the blood flow therefrom and permit the adhesive surfaceof the strip to adhere to the skin and hold the bandage in place. Thebandage may be provided in a closed sterile receptacle or container orthe like.

In one embodiment, the invention provides a hemostatic sponge that canbe applied to a bleeding wound to clot blood and control bleeding. Sucha sponge comprises a substrate and a hemostatic composition of theinvention disposed on a first surface of the substrate or dispersed inthe substrate. Another type of sponge has first and second substrates. Ahemostatic composition of the invention is applied to the firstsubstrate, and the second substrate is placed on the hemostaticcomposition. When this sponge is used to treat a bleeding wound,applying the sponge causes at least a portion of the hemostatic materialto come into contact with blood through at least one of the substrates.The hemostatic sponge may comprise a film and a hemostatic compositionof the invention incorporated into the film; a substrate, a hemostaticcomposition of the invention disposed on the substrate, and a filmdisposed over the hemostatic composition of the invention; or ahemostatic composition of the invention sandwiched between twosubstrates.

Thus, the composition can be used in solid form (e.g., retained in amesh or in a film), or it can be used in powder form (e.g., deposited ona fibrous substrate to form a gauze or a sponge).

In one embodiment, the combination of agents disclosed herein greatlyenhances blood clotting, inhibits microbial infection, and/oraccelerates wound healing, and may be combined with a covering orcarrier (support) such as a bandage, cotton gauze and the like. In oneembodiment, a wound treated with a composition of the invention issubsequently covered with a suitable wound covering or dressing. Inanother embodiment, a wound covering or dressing is impregnated orcoated with a dry powder form of a composition of the invention andapplied to the wound. Thus, the present invention can also be practicedin conjunction with wound coverings, dressings, and protectivematerials, such as bandages, cotton gauze, and the like.

The invention also concerns kits comprising in one or more containers orpackages having a plurality of components for a composition of theinvention. In one embodiment, a composition of the invention is packagedin a container that is designed in a manner so as to preserve theanhydrous nature of the composition until the container is opened. A kitof the invention can also comprise a container having a quantity ofsuitable powder or spray liquid or aqueous media, for application to awound. In one embodiment, the powder spray or liquid or aqueous media isprovided in sterile form. A kit of the present invention can alsocomprise a wound covering, dressing, or other wound or surgical siteprotective material, e.g., one maintained in sterile form until thepackage or container is opened for use.

In one embodiment, a kit comprises a dressing that includes a pad thatcontains a composition of the invention within and/or on the surface ofthe pad. In one embodiment, the pad is composed of porous foam that issufficiently open to allow a free flow of powder to fill the voids inthe porous foam. The open voids can either be random (like a foam airconditioning filter) or organized into tunnels. The tunnels can keepcompositions from mixing until needed. The tunnels can be round holes orgeometric shapes. Around the perimeter of the randomly open foam a lessporous border may be used to contain the composition. The pad can bedesigned so that lateral pressure can compress the foam or tunnels andhold the composition in place for inverted application.

In another embodiment, a kit comprises a dressing having a pad withfibers perpendicularly oriented to the plane of the pad, wherein thefibers can hold and release a composition of the present invention. Thedressing can be provided with or without an integrated foam or fabric orsubstrate backing. The dressing can be pre-loaded with a composition ofthe present invention. The dressing can be of a design wherein thefibers remain attached to the dressing during and/or after applicationto a wound or surgical site.

In one embodiment, a kit comprises a wound dressing with a flocked padwherein the pad has a foam (e.g., polyurethane) portion and a flockedfibers portion. In one embodiment, the foam portion is a porous foam asdescribed above. In this embodiment, a composition of the invention canbe loaded onto the side of the foam opposite that of the fibers and thecomposition could then travel or flow through the foam and onto thefibers. The fibers can be attached to the foam portion and can be made,for example, out of calcium alginate. The fibers can be a woven ornon-woven material. The fibers can be composed of any suitable materialsuch as cotton, wool, etc. In one embodiment, the fibers are composed ofa velvet fabric. The fibers can be coated or flocked with a compositionof the present invention.

Optionally, the fibers can be composed of dissolvable material (e.g.,polyvinyl alcohol) or a biodegradable material (e.g., starch, calciumalginate, polysaccharides, etc.). In one embodiment, the fibers can becomposed of a material that can dissolve in a solution, such as a salinesolution. In another embodiment, the fibers themselves do not dissolvein solution but are attached to the pad portion via a substance ormaterial that itself can dissolve in solution. This permits a solutionto be contacted with a dressing that has been applied to a site whereblood has coagulated and formed a scab, wherein the fibers dissolve orthe attachment dissolves and the pad portion of the dressing can then beeasily removed without ripping the scab off the wound.

Compositions of the invention may be stored under substantiallyanhydrous conditions. Compositions of the invention can be provided in asterile form.

Compositions of the subject invention can also comprise additionaloptional compounds or agents that provide for anti-microbial, analgesicor anesthetic, increased absorptive, and/or increased wound healingproperties.

The dosage or amount of the components of a composition of the inventionto be typically administered can be readily determined and will bedependent on various factors, such as the size and type of wound, theamount of blood or fluid present in the wound, and physicalcharacteristics of the patient, as well as other drugs or treatments thepatient is receiving.

The compositions of the invention are easy to use and to apply to awound, likely cause no irritation or allergic responses, and absorbwound exudates (which reduces odors and microbial action at the woundsite) and so may also be used to treat lesions, trauma, injuries,incisions, and/or burns wherein stopping or slowing the flow of bloodfrom a wound, incision, or medical treatment site is indicated.

Following application of a composition of the invention, e.g., a sprayor gel, the wound may be left exposed to the air, or the wound mayoptionally be covered with a bandage or other suitable wound covering,e.g., one that includes a composition of the invention.

Exemplary Compositions

Disclosed herein are hemostatic devices and hemostatic agents that areapplicable to bleeding wounds to promote hemostasis. In one embodiment,the hemostatic agents generally include absorbent agents such assilica-based materials that, when brought into contact with a bleedingwound, can minimize or stop blood flow by absorbing at least portions ofthe liquid phases of the blood, thereby facilitating clotting. In oneembodiment, the absorbent agent of the invention is mixed with orotherwise used in conjunction with other materials to provide additionalclotting functions and/or improved efficacy, including a blood vesselconstricting agent, and optionally agents that provide an antisepticenvironment at the wound site or to provide functions that aresupplemental to the clotting functions, including, but are not limitedto, pharmaceutically-active compositions such as antibiotics, antifungalagents, antimicrobial agents, anti-inflammatory agents, analgesics,antihistamines (e.g., cimetidine, chloropheniramine maleate,diphenhydramine hydrochloride, and promethazine hydrochloride),compounds containing silver or copper ions, combinations of theforegoing, and the like. Other materials that can be incorporated toprovide additional hemostatic functions include ascorbic acid,tranexamic acid, rutin, and thrombin. Botanical agents having desirableeffects on the wound site may also be added.

In one embodiment, the substrate is an absorbent gauze material thatdefines a matrix. Other materials from which the substrate may befabricated include woven fabric, non-woven fabric, paper (e.g., kraftpaper and the like), and cellulose material (e.g., cotton in the formsof balls, swabs, and the like), as well as other materials such asrayon/polyester cellulose blends and the like are also within the scopeof the present invention.

In one embodiment, a composition of the present invention is woven intothe fibers of the substrate. For example, a composition which includesan effective amount of aluminum sulfate and mullite, and whichoptionally includes other ingredients such as fibrin, a local anestheticagent, and/or an antiseptic agent, may be woven into the fibers of anabsorbent tissue/paper product. The product may then be used in woundcleaning and to blot up blood resulting from minor cuts or scrapes. Itmay also be used in a bandage or other wound dressing to facilitateblood clotting, to provide an anesthetic effect, and/or to provide anantiseptic effect.

In one embodiment, the invention provides a composition which includesan effective amount of aluminum sulfate and mullite, optionally havingisolated fibrin, or isolated fibrinogen and isolated thrombin, and alsooptionally a local anesthetic agent and/or an antiseptic agent. In oneembodiment, a composition of the invention includes an absorbent agent(e.g. mullite) and a blood vessel constricting agent (e.g., aluminumsulfate or caffeine). In one embodiment, a composition of the inventionincludes an absorbent agent (e.g. mullite), a blood vessel constrictingagent (e.g., aluminum sulfate or caffeine), and a local (e.g., topical)anesthetic agent. In one embodiment, a composition of the inventionincludes an absorbent agent (e.g. mullite), a blood vessel constrictingagent (e.g., aluminum sulfate or caffeine), a local anesthetic agent andan antiseptic agent. In one embodiment, a composition of the inventionincludes an absorbent agent (e.g. mullite), a blood vessel constrictingagent (e.g., aluminum sulfate or caffeine), isolated fibrinogin andisolated thrombin (or isolated fibrin). In one embodiment, a compositionof the invention includes an absorbent agent (e.g. mullite), a bloodvessel constricting agent (e.g., aluminum sulfate or caffeine), isolatedfibrinogin and isolated thrombin (or isolated fibrin), and a localanesthetic agent. In one embodiment, a composition of the inventionincludes an absorbent agent (e.g. mullite) a blood vessel constrictingagent (e.g., aluminum sulfate or caffeine), isolated fibrinogin andisolated thrombin (or isolated fibrin), a local anesthetic agent and anantiseptic agent. In one embodiment, the invention provides a bandage,gel or spray having a composition of the invention.

In one embodiment, a composition of the invention has a blood vesselconstricting agent (e.g., aluminum sulfate or caffeine) and a local(e.g., topical) anesthetic agent. In one embodiment, a composition ofthe invention has a blood vessel constricting agent (e.g., aluminumsulfate or caffeine), a local anesthetic agent and an antiseptic agent.In one embodiment, a composition of the invention has a blood vesselconstricting agent (e.g., aluminum sulfate or caffeine), isolatedfibrinogin and isolated thrombin (or isolated fibrin). In oneembodiment, a composition of the invention has a blood vesselconstricting agent (e.g., aluminum sulfate or caffeine), isolatedfibrinogin and isolated thrombin (or isolated fibrin), and a localanesthetic agent. In one embodiment, a composition of the invention hasa blood vessel constricting agent (e.g., aluminum sulfate or caffeine),isolated fibrinogin and isolated thrombin (or isolated fibrin), a localanesthetic agent and an antiseptic. In one embodiment, the inventionprovides a bandage, gel or spray having a composition of the invention.

In one embodiment, an absorbent agent (e.g. mullite) and a blood vesselconstricting agent (e.g., aluminum sulfate and/or caffeine) are in aratio of 1:1 or 2:1 by volume. In one embodiment, an absorbent agent(e.g. mullite), a blood vessel constricting agent (e.g., aluminumsulfate and/or caffeine), plus a local anesthetic agent such aslidocaine, tetracaine, or benzocaine or prilocaine, are employed in acomposition, e.g., one in which the formulation ranges from 1:1 to 2:1absorbent agent to blood vessel constricting agent, with an effectiveamount of a local anesthetic agent. In one embodiment, an absorbentagent (e.g. mullite), a blood vessel constricting agent (e.g., aluminumsulfate and/or caffeine), a local anesthetic agent such as lidocaine,tetracaine, or benzocaine, and an antimicrobial, such as neomycinsulfate, polymyxin B, bacitracin zinc, pramoxine or prilocaine, areemployed in a composition of the invention. In one embodiment, anabsorbent agent (e.g. mullite) a blood vessel constricting agent (e.g.,aluminum sulfate and/or caffeine), and isolated fibrinogin and isolatedthrombin (or isolated fibrin) are employed in a composition, e.g., onein which the formulation ranges from 1:1 to 2:1 absorbent agent to bloodvessel constricting agent, with an effective amount of fibrin. In oneembodiment, an absorbent agent, a blood vessel constricting agent,isolated fibrinogin and thrombin (or isolated fibrin), and a localanesthetic agent such as lidocaine, tetracaine, or benzocaine orprilocaine, are employed, in which the formulation ranges from 1:1 to2:1 absorbent agent to blood vessel constricting agent, with effectiveamounts of fibrin and a local anesthetic agent. In one embodiment, thecomposition comprises an absorbent agent (e.g. mullite), a blood vesselconstricting agent (e.g., aluminum sulfate and/or caffeine), isolatedfibrinogin and isolated thrombin (or isolated fibrin), a localanesthetic agent such as lidocaine, tetracaine, or benzocaine orprilocaine, and an antimicrobial antiseptic such as neomycin sulfate,polymyxin B, bacitracin zinc, or pramoxine, are employed. An exemplaryformulation range is from 1:1 to 2:1 absorbent agent to blood vesselconstricting agent, with effective amounts of fibrin, a local anestheticagent, and an antiseptic agent.

In one embodiment, to deliver the therapeutic agents, a powder may beused to quickly clot blood when applied directly to minor cut orscrapes. In one embodiment, a powder is available in spray form. In oneembodiment, the powder is woven in fibers of pad in adhesive bandage orgauze. Other substances may also be woven into fibers of pad in adhesivebandages or gauze or fibers of paper like tissue to be used for blotting(added to facial tissue or smaller tissues similar to those used forfacial oil absorbing). In one embodiment, a component may be adhered toa pad in adhesive bandage using bonding agent (e.g., glycerin). In oneembodiment, the substance added to an antiseptic dispensing device orcomposition (gel, liquid, or spray). In one embodiment, a powder iscompressed into stick form or into a mold that is packaged along with adisposable applicator. In one embodiment, the composition is availablein a snap q-tip form (plastic tube in the middle, snapped releasessubstance to cotton tip for application).

To prepare compositions in accordance with the present invention, theindividual components were combined to result in the composition. Thecomponents may be combined using any method that does not negativelyaffect the functionality of each component and provides uniform ornearly uniform distribution of the components in the composition, suchas but not limited to mixing under shear forces or under agitation. Thecomponents used in the composition are of pharmaceutically or medicallyacceptable purity.

EXAMPLES: COMPOSITIONS INCLUDING KAOLIN Example 1: Kaolin and AluminumSulfate

Testing was conducted using a powder composition including a mixture ofkaolin (i.e. aluminum silicate hydroxide) and aluminum sulfate, whereinthe kaolin and aluminum sulfate were present at a 1:1 ratio by volume.Cuts similar in size and depth were made to the right and left indexfingers of a human subject using a razor blade. The powder compositionwas applied to a bandage, which was then placed over the cut on the leftindex finger. A plain bandage, which did not include the powdercomposition, was placed over the cut on the right index finger. Both ofthe bandages were removed after 1 minute and the cuts were visuallyinspected. After 1 minute, the cut on the left index finger, to which abandage including the powder composition had been applied, had stoppedbleeding entirely. However, after the same amount of time, the cut onthe right index finger, to which a bandage without the powdercomposition had been applied, continued to bleed. Similar results werealso obtained by applying the powder composition to cuts on the ankleand leg of a human subject.

Further testing was conducted by applying the powder composition, whichincluded a mixture of kaolin and aluminum sulfate at a 1:1 ratio byvolume, directly to cuts on a human subject without using a bandage.This further testing showed that the application of the powdercomposition without a bandage was also effective in stopping thebleeding from cuts, and in facilitating the healing of wounds.

To determine whether another powder composition that could absorbmoisture would be effective in stopping the bleeding from cuts, a sampleof flour was applied to a cut on a human subject. The testing showedthat the application of flour was not effective in stopping the bleedingfrom cuts.

Testing was also conducted using kaolin and aluminum sulfateindividually to treat cuts on a human subject. It was unexpectedly foundthat the combination of kaolin and aluminum sulfate was significantlymore effective in healing wounds than either of these components alone.While not intending to be bound by theory, it is believed that thecombination of kaolin and aluminum sulfate works synergistically to stopblood flow by removing blood from the wound, constricting blood vessels,and stimulating the coagulation cascade to produce blood clotting.

EXAMPLES: COMPOSITIONS INCLUDING MULLITE

The following examples involve compositions including mullite andaluminum sulfate. The mullite used in these examples had the formulaAl₆O₁₃Si₂, and was obtained from Sigma-Aldrich Corp., St. Louis, Mo.,United States. The aluminum sulfate was obtained from Chemistrystore.comInc., Cayce, S.C., United States. The percentages of mullite andaluminum sulfate reported in the following examples, such as 50% mulliteand 50% aluminum sulfate, are percentages reported by volume.Specifically, to prepare a 50% mullite and 50% aluminum sulfate mixture,equal volumes of each component were used. A volume of approximately 3tablespoons, or about 44.4 mL, of each component was used to prepare asmall batch of a 50% mullite and 50% aluminum sulfate mixture. Threesmall batches were combined to prepare a large batch of approximately 18tablespoons, or about 266.4 mL.

To prepare each mixture, the mullite and aluminum sulfate were initiallymixed together by hand using a spoon, and then placed in a closedcontainer and agitated for approximately one minute. Each mixture wasvisually inspected to confirm that it was substantially homogeneous.

Example 2: Mullite and Aluminum Sulfate

Testing was conducted using powder compositions including mullite andaluminum sulfate. Three different compositions were tested: composition1, which was comprised of 25% mullite and 75% aluminum sulfate;composition 2, which was comprised of 50% mullite and 50% aluminumsulfate; and composition 3, which was comprised of 75% mullite and 25%aluminum sulfate. Tests were conducted by applying the powdercompositions to cuts on animal subjects (rabbits and rats). Theincisions were each 1 cm in length, and were made using a surgicalknife. Each incision was made to a depth at which consistent bleedingoccurred along the length of the incision. After each incision was made,the incision was blotted once, and then a timer clock was started. Apowder composition was then applied to the incision. A sufficient amountof powder composition was used to cover the entire incision. It wasfound that 1/16 (0.0625) of a teaspoon of the powder composition, orabout 0.308 mL, was sufficient, although it is contemplated that more orless may be used depending on the size and depth of the incision. Theamount of time from the starting of the timer clock to the cessation ofbleeding was measured. The cessation of bleeding was determined byvisual inspection.

Control tests were also conducted on animal subjects (rabbits and rats).In the control tests, after each incision was made, the incision wasblotted once and then a timer clock was started. The amount of time fromthe starting of the timer clock to the cessation of bleeding wasmeasured. The cessation of bleeding was determined by visual inspection.In the control tests, no composition was applied to the incisions.

Each of the three compositions were effective in quickly stopping thebleeding from minor cuts. The composition which caused a cessation inbleeding in the shortest amount of time was composition 2, comprised of50% mullite and 50% aluminum sulfate. When composition 2 was applied tominor cuts, bleeding stopped in an average amount of time of 17 seconds.Generally, the bleeding stopped almost immediately when composition 2was applied, but because the timer clock was started just prior to theapplication of the composition, the measured amount of time included thetime required to apply the composition. In contrast, when the controltests were conducted, bleeding stopped in an average of 1 minute and 34seconds. Therefore, the test results showed that there was an 82%improvement in healing rate when composition 2 was used, in comparisonto the control tests.

Accordingly, the testing showed that a composition comprising mulliteand aluminum sulfate significantly shortened the amount of time requiredto stop the bleeding from minor cuts. Of the compositions tested, thecomposition which stopped the bleeding from cuts most quickly was acomposition including mullite and aluminum sulfate in a 1:1 ratio byvolume. While not intending to be bound by theory, it is believed thatthe combination of mullite and aluminum sulfate works synergistically tostop blood flow by removing moisture from the wound, constricting bloodvessels, and stimulating the coagulation cascade to produce bloodclotting.

Example 3: Mullite/Aluminum Sulfate Composition Compared to CommerciallyAvailable Styptic Powder

Testing was conducted to compare a mullite/aluminum sulfate compositionmade in accordance with the present invention to a commerciallyavailable styptic powder. The mullite/aluminum sulfate composition was apowder composition comprising 50% mullite and 50% aluminum sulfate. Thecommercially available styptic powder was Kwik Stop® styptic powder,which is indicated for use on animals, and is available from Gimborn PetSpecialties, Atlanta, Ga., United States. Tests were conducted byapplying the powder compositions to cuts on animal subjects (rabbits andrats). The incisions were each 1 cm in length, and were made using asurgical knife. Each incision was made to a depth at which consistentbleeding occurred along the length of the incision. After each incisionwas made, the incision was blotted once, and then a timer clock wasstarted. A powder composition was then applied to the incision. Asufficient amount of powder composition was used to cover the entireincision. It was found that 1/16 (0.0625) of a teaspoon, or about 0.308mL, was sufficient, although it is contemplated that more or less may beused depending on the size and depth of the incision. The amount of timefrom the starting of the timer clock to the cessation of bleeding wasmeasured. The cessation of bleeding was determined by visual inspection.

Control tests were conducted on the same animal that was treated withthe Kwik Stop® styptic powder. In the control tests, after each incisionwas made, the incision was blotted once and then a timer clock wasstarted. The amount of time from the starting of the timer clock to thecessation of bleeding was measured. The cessation of bleeding wasdetermined by visual inspection. In the control tests, no compositionwas applied to the incisions.

The composition which caused a cessation in bleeding in the shortestamount of time was the mullite/aluminum sulfate composition. When thiscomposition was applied to minor cuts, bleeding stopped in an averageamount of time of 17 seconds. In contrast, when the Kwik Stop® stypticpowder was applied to a minor cut, bleeding stopped in an average amountof time of 35 seconds. When the control test was conducted, bleedingstopped in an average amount of time of 48 seconds. Therefore, the testresults showed that there was a 51% improvement in healing rate whencomposition 2 was used, in comparison to Kwik Stop® styptic powder. Thetest results also showed that, in comparison to the control tests, therewas a 27% improvement in healing rate when Kwik Stop® styptic powder wasused, and a 65% improvement in healing rate when composition 2 was used.

Example 4: Use of Mullite/Aluminum Sulfate Composition to ImproveHealing Over Time

Testing was conducted to determine whether a mullite/aluminum sulfatecomposition made in accordance with the present invention would improvehealing over time, in comparison to a commercially available stypticpowder. The mullite/aluminum sulfate composition was a powdercomposition comprising 50% mullite and 50% aluminum sulfate. Thecommercially available styptic powder was Kwik Stop® styptic powder,which is indicated for use on animals, and is available from Gimborn PetSpecialties, Atlanta, Ga., United States. Tests were conducted byapplying the powder compositions to incisions on the backs of animalsubjects (rabbits). The incisions were each 1 cm in length, and weremade using a surgical knife. Each incision was made to a depth at whichconsistent bleeding occurred along the length of the incision. Asufficient amount of powder composition was applied to the incision tocover the entire wound. It was found that 1/16 (0.0625) of a teaspoon,or about 0.308 mL, was sufficient, although it is contemplated that moreor less may be used depending on the size and depth of the incision. Acontrol test was also conducted, in which no composition was applied toan incision on the back of an animal (rabbit) subject. The animalsubjects were then observed for a 14 day period and monitored forhealing side effects, including discharge, bruising, swelling, increasedtemperature at the wound site, and erythema.

The healing side effects observed were as follows. In the control test,very mild swelling was present on day one, and mild erythema was presenton days one through ten. In the test in which Kwik Stop® styptic powderwas applied, mild swelling was present on days two through seven, andmild erythema was present on days one through eight. In the test inwhich the mullite/aluminum sulfate composition was applied, very mildswelling and mild erythema were present on day one. Therefore, themullite/aluminum sulfate composition reduced the duration of healingside effects, in comparison to the Kwik Stop® styptic powder and incomparison to the results of a control test.

Example 5: Use of Mullite/Aluminum Sulfate Composition to Stop Bleedingfrom a Major Artery

Testing was conducted to determine whether a mullite/aluminum sulfatecomposition made in accordance with the present invention would beeffective in stopping the bleeding from an incision of a major artery.The mullite/aluminum sulfate composition was a powder compositioncomprising 50% mullite and 50% aluminum sulfate. The test of themullite/aluminum sulfate composition was conducted by applying thepowder composition to an incision of the auricular artery of a rabbitand measuring the amount of time required for the cessation of activebleeding. The auricular artery was cut through a cross section to createthe incision.

No pressure was added to the wound. A sufficient amount of powdercomposition was used to cover the entire incision. It was found that1/16 (0.0625) of a teaspoon, or about 0.308 mL, was sufficient, althoughit is contemplated that more or less may be used depending on the sizeand depth of the incision. The amount of time was measured by starting atimer clock, applying the powder composition to the wound, blotting thewound after 20 seconds had elapsed, reapplying the powder composition,and stopping the clock when active bleeding from the artery ceased. Thetotal amount of time measured, from the time the clock was started tothe time active bleeding ceased, as determined by visual inspection, was2 minutes and 15 seconds. Accordingly, the testing found that themullite/aluminum sulfate composition of the present invention was ableto effect the clotting of blood from serious wounds.

For comparison, a test using fibrin was also conducted. The fibrin was acommercially available lyophilized fibrin in powder form. The fibrintest was conducted by applying the lyophilized fibrin to an incision ofthe auricular artery of a rabbit and measuring the amount of timerequired for the cessation of active bleeding. The auricular artery wascut through a cross section to create the incision. No pressure wasadded to the wound. A sufficient amount of powder composition was usedto cover the entire incision. It was found that 1/16 (0.0625) of ateaspoon, or about 0.308 mL, was sufficient, although it is contemplatedthat more or less may be used depending on the size and depth of theincision. The amount of time was measured by blotting the wound,starting the timer clock, applying the fibrin to the wound, and stoppingthe clock when active bleeding from the artery ceased. The total amountof time measured, from the time the clock was started to the time activebleeding ceased, as determined by visual inspection, was 1 minute and 24seconds.

In the fibrin test, as discussed above, the fibrin remained on the woundfor the duration of the test, while in the mullite/aluminum sulfatetest, the composition was not on the wound for the duration of the testbecause the composition was removed and reapplied. Therefore, eventhough a greater amount of time was measured in the mullite/aluminumsulfate test, the testing showed that the effectiveness of themullite/aluminum sulfate composition was similar to that of fibrin, inclotting the blood from a major artery. These results are significantbecause the fibrin used in the testing cost more than 1,000 times asmuch as the mullite/aluminum sulfate composition used in the testing.

Example 6: Use of Mullite/Aluminum Sulfate/Fibrin Composition

Testing was conducted to determine whether adding fibrin to amullite/aluminum sulfate composition of the present invention wouldimprove the effectiveness of the composition. The mullite/aluminumsulfate composition was a powder composition comprising 50% mullite and50% aluminum sulfate. Fibrin in freeze dried form was added to thiscomposition at a 1:1 ratio by volume, resulting in a compositioncomprising 25% mullite, 25% aluminum sulfate, and 50% fibrin. Both themullite/aluminum sulfate composition without added fibrin and themullite/aluminum sulfate composition with added fibrin were tested.Tests were conducted by applying the powder compositions to minor cutson animal subjects (rabbits and rats). The incisions were each 1 cm inlength, and were made using a surgical knife. Each incision was made toa depth at which consistent bleeding occurred along the length of theincision. After each incision was made, the incision was blotted once,and then a timer clock was started. A powder composition was thenapplied to the incision. A sufficient amount of powder composition wasused to cover the entire incision. It was found that 1/16 (0.0625) of ateaspoon, or about 0.308 mL, was sufficient, although it is contemplatedthat more or less may be used depending on the size and depth of theincision. The amount of time from the starting of the timer clock to thecessation of active bleeding was measured. The cessation of bleeding wasdetermined by visual inspection.

Both of the compositions were effective in quickly stopping the bleedingfrom minor cuts. When the mullite/aluminum sulfate composition withoutadded fibrin was applied to minor cuts, bleeding stopped in an averageamount of time of 17 seconds. When the mullite/aluminum sulfatecomposition with added fibrin was applied to minor cuts, bleedingstopped in an average amount of time of 13 seconds.

Therefore, the addition of fibrin to the mullite/aluminum compositiondid not significantly improve effectiveness in stopping the bleedingfrom minor cuts.

Testing was also conducted to determine whether adding fibrin to amullite/aluminum sulfate composition would improve healing over time.The mullite/aluminum sulfate composition was a powder compositioncomprising 50% mullite and 50% aluminum sulfate. Fibrin in freeze driedform was added to this composition at a 1:1 ratio by volume, resultingin a composition comprising 25% mullite, 25% aluminum sulfate, and 50%fibrin. Both the mullite/aluminum sulfate composition without addedfibrin and the mullite/aluminum sulfate composition with added fibrinwere tested. Tests were conducted by applying the powder compositions toincisions on the backs of animal subjects (rabbits). The animal subjectswere then monitored for healing side effects, including discharge,bruising, swelling, increased temperature at the wound site, anderythema.

In the test of the mullite/aluminum sulfate composition without addedfibrin, very mild swelling an mild erythema were present on day one. Nohealing side effects were observed after day one. In the test of themullite/aluminum sulfate composition with added fibrin, discharge andswelling were observed on days one and two, and erythema was observed ondays one through three. Therefore, fewer healing side effects wereobserved when the mullite/aluminum sulfate composition without addedfibrin was used, in comparison to the composition with added fibrin.

All publications, patents and patent applications are incorporatedherein by reference. While in the foregoing specification, thisinvention has been described in relation to certain preferredembodiments thereof, and many details have been set forth for purposesof illustration, it will be apparent to those skilled in the art thatthe invention is susceptible to additional embodiments and that certainof the details herein may be varied considerably without departing fromthe basic principles of the invention.

What is claimed is:
 1. A composition for wound healing, comprising: asubstantially homogeneous mixture comprising an amount of mullite,wherein the amount of mullite is effective to promote blood clotformation, and aluminum sulfate, wherein the composition is in powder orliquid form.
 2. The composition of claim 1, further comprising a localanesthetic agent.
 3. The composition of claim 1, further comprising ananalgesic agent.
 4. The composition of claim 1, further comprising anantiseptic agent.
 5. The composition of claim 4, wherein the antisepticagent is an antimicrobial agent.
 6. The composition of claim 1, whereinthe aluminum sulfate and mullite are present in a ratio of at least 1:3by volume.
 7. The composition of claim 1, wherein the aluminum sulfateand mullite are present in a ratio of at least 1:2 by volume.
 8. Thecomposition of claim 1, wherein the aluminum sulfate and mullite arepresent in a ratio of at least 1:1 by volume.
 9. A hemostatic devicecomprising a wound dressing and the composition of claim
 1. 10. Thehemostatic device of claim 9, wherein the wound dressing is a bandage.11. A method for promoting blood clot formation, comprising: providing acomposition in powder or liquid form, the composition comprising asubstantially homogeneous mixture comprising an amount of mullite,wherein the amount of mullite is effective to promote blood clotformation, and aluminum sulfate; and contacting a wound on the skin of amammal with the composition.
 12. The method of claim 11, wherein thecomposition further comprises a local anesthetic agent.
 13. The methodof claim 11, wherein the composition further comprises an analgesicagent.
 14. The method of claim 11, wherein the composition furthercomprises an antiseptic agent.
 15. The method of claim 14, wherein theantiseptic agent is an antimicrobial agent.
 16. The method of claim 11,wherein the aluminum sulfate and mullite in the composition are presentin a ratio of at least 1:3 by volume.
 17. The method of claim 11,wherein the aluminum sulfate and mullite in the composition are presentin a ratio of at least 1:2 by volume.
 18. The method of claim 11,wherein the aluminum sulfate and mullite in the composition are presentin a ratio of at least 1:1 by volume.
 19. The method of claim 11,wherein the composition is applied to a wound dressing prior tocontacting the wound on the skin of the mammal with the composition. 20.The method of claim 19, wherein the wound dressing is a bandage.